2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T6e0,Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially fatal multisystem complication of hematopoietic cell transplantation for which there is no approved treatment. In a single-arm study (NCT02222545), narsoplimab treatment for TA-TMA demonstrated a median overall survival (OS) of 274 days from date of diagnosis. Here, we compare OS observed in 2 cohorts treated with narsoplimab to OS in a well-matched external control to test survival benefit in patients with high-risk TA-TMA. OS in patients (aged ≥16 years) with high-risk TA-TMA treated with narsoplimab in a single-arm, open-label study (NCT02222545) or in the narsoplimab expanded access program (EAP; NCT04247906) was compared with OS in a control group with high-risk TA-TMA from the Kyoto Stem Cell Transplantation Group (KSCTG) registry. Narsoplimab-treated patients in the single-arm study (N = 28) had a fourfold reduction in risk of mortality compared with patients from the KSCTG registry (N = 111; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.19, 0.34; P < .0001). Similarly, in high-risk patients treated with narsoplimab in the EAP (N = 49), mortality risk was significantly lower than among high-risk patients from the KSCTG registry (N = 121; HR 0.38; 95% CI 0.28, 0.51; P < .0001). When narsoplimab-treated patients from the single-arm study and the EAP (N = 77) were compared with KSCTG patients, the HR for mortality was 0.28 (95% CI, 0.22, 0.37; P < .0001). In conclusion, in patients with high-risk TA-TMA, narsoplimab treatment significantly reduced mortality relative to a well-matched external control group who did not receive narsoplimab. These results support narsoplimab as a potential therapeutic option for TA-TMA.31:T77b, Abstract Hematopoietic stem cell transplant–associated thrombotic microangiopathy (TA-TMA) is a potentially fatal multisystem complication of hematopoietic cell transplantation for which there is no approved treatment. In a single-arm study (NCT02222545), narsoplimab treatment for TA-TMA demonstrated a median overall survival (OS) of 274 days from date of diagnosis. Here, we compare OS observed in 2 cohorts treated with narsoplimab to OS in a well-matched external control to test survival benefit in patients with high-risk TA-TMA. OS in patients (aged ≥16 years) with high-risk TA-TMA treated with narsoplimab in a single-arm, open-label study (NCT02222545) or in the narsoplimab expanded access program (EAP; NCT04247906) was compared with OS in a control group with high-risk TA-TMA from the Kyoto Stem Cell Transplantation Group (KSCTG) registry. Narsoplimab-treated patients in the single-arm study (N = 28) had a fourfold reduction in risk of mortality compared with patients from the KSCTG registry (N = 111; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.19, 0.34; P < .0001). Similarly, in high-risk patients treated with narsoplimab in the EAP (N = 49), mortality risk was significantly lower than among high-risk patients from the KSCTG registry (N = 121; HR 0.38; 95% CI 0.28, 0.51; P < .0001). When narsoplimab-treated patients from the single-arm study and the EAP (N = 77) were compared with KSCTG patients, the HR for mortality was 0.28 (95% CI, 0.22, 0.37; P < .0001). In conclusion, in patients with high-risk TA-TMA, narsoplimab treatment significantly reduced mortality relative to a well-matched external control group who did not receive narsoplimab. These results support narsoplimab as a potential therapeutic option for TA-TMA. 32:Ta56,Intravitreal complement inhibitors injections (IVCIs) slowed progression of geographic atrophy (GA) lesions in several registration phase 3 trials although without benefit for prespecified secondary functional vision outcomes. Patient acceptability of these therapies needs further exploration. To quantify the acceptability of IVCI therapy to United Kingdom patients with GA, assuming vision outcome benefits are expected. This cross-sectional study took place at 9 geographically dispersed UK National Health Service centers from April 2023 to April 2024 among 153 participants with treatment-naive GA in at least 1 eye. GA in at least 1 eye. Main outcomes were (1) acceptability of IVCI therapy based on completion of validated acceptability questionnaire. Participants were provided with a treatment information leaflet coproduced by a patients with lived experience of GA to inform them about the risks and benefits of IVCI for GA, assuming there were vision outcome benefits to this treatment and (2) response to the EuroQol 5-dimension with a vision bolt-on questionnaire to assess general health and vision-related quality of life. Spearman rank correlations and χ2 tests were used to explore associations between acceptability levels and specific ocular and sociodemographic characteristics. A total of 153 participants were recruited (93 [60%] women; mean [SD] age, 82 [7]), 57 (38%) of whom had bilateral foveal involvement. Median (IQR) visual acuity with habitual correction in the better-seeing eye and in eyes where neither eye was better or worse was logMAR, 0.30 (0.14-0.54; approximate Snellen equivalent, 20/40) and 0.47 (0.14-0.84; approximate Snellen equivalent, 20/63), respectively. Among the 153 participants, 81 (53%; 95% CI, 45-61) reported IVCIs were very much or extremely acceptable under the theoretical scenarios provided. The proportion finding IVCIs acceptable rose to 82% (95% CI, 76-88) when including those who rated prospective treatment as moderately acceptable. Belief in the perceived effectiveness of the treatment (ρ, 0.52; 95% CI, 0.40-0.63; P < .001) and confidence in their ability to attend the eye clinic regularly (ρ, 0.51; 95% CI, 0.38-0.62; P < .001) correlated with overall acceptability. IVCI therapy for GA may be acceptable to most UK patients with GA under the assumption that there are vision outcome benefits to this treatment. While current treatments do not result in vision outcome benefits, perceived effectiveness by patients was associated with acceptability, emphasizing the desire to quantify vision functional benefit concomitant with anatomical slowing of progression.33:T106a, Importance Intravitreal complement inhibitors injections (IVCIs) slowed progression of geographic atrophy (GA) lesions in several registration phase 3 trials although without benefit for prespecified secondary functional vision outcomes. Patient acceptability of these therapies needs further exploration. Objective To quantify the acceptability of IVCI therapy to United Kingdom patients with GA, assuming vision outcome benefits are expected. Design, Setting, and Participants This cross-sectional study took place at 9 geographically dispersed UK National Health Service centers from April 2023 to April 2024 among 153 participants with treatment-naive GA in at least 1 eye. Exposures GA in at least 1 eye. Main Outcomes and Measures Main outcomes were (1) acceptability of IVCI therapy based on completion of validated acceptability questionnaire. Participants were provided with a treatment information leaflet coproduced by a patients with lived experience of GA to inform them about the risks and benefits of IVCI for GA, assuming there were vision outcome benefits to this treatment and (2) response to the EuroQol 5-dimension with a vision bolt-on questionnaire to assess general health and vision-related quality of life. Spearman rank correlations and χ 2 tests were used to explore associations between acceptability levels and specific ocular and sociodemographic characteristics. Results A total of 153 participants were recruited (93 [60%] women; mean [SD] age, 82 [7]), 57 (38%) of whom had bilateral foveal involvement. Median (IQR) visual acuity with habitual correction in the better-seeing eye and in eyes where neither eye was better or worse was logMAR, 0.30 (0.14-0.54; approximate Snellen equivalent, 20/40) and 0.47 (0.14-0.84; approximate Snellen equivalent, 20/63), respectively. Among the 153 participants, 81 (53%; 95% CI, 45-61) reported IVCIs were very much or extremely acceptable under the theoretical scenarios provided. The proportion finding IVCIs acceptable rose to 82% (95% CI, 76-88) when including those who rated prospective treatment as moderately acceptable. Belief in the perceived effectiveness of the treatment (ρ, 0.52; 95% CI, 0.40-0.63; P &lt; .001) and confidence in their ability to attend the eye clinic regularly (ρ, 0.51; 95% CI, 0.38-0.62; P &lt; .001) correlated with overall acceptability. Conclusions and Relevance IVCI therapy for GA may be acceptable to most UK patients with GA under the assumption that there are vision outcome benefits to this treatment. While current treatments do not result in vision outcome benefits, perceived effectiveness by patients was associated with acceptability, emphasizing the desire to quantify vision functional benefit concomitant with anatomical slowing of progression. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Complement Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Complement Inhibitor (modality). 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clinical use should be reassessed pending regulatory decision.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.06.008","tag_type":"warning","value":"Several sample sizes cited (e.g., VALIANT n=124, APPEAR-C3G n=74, APPLAUSE-IgAN n=250) are from interim analyses, not final trial results — effect sizes may change.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.06.008","tag_type":"warning","value":"Study design tag reflects that this is a narrative Core Curriculum review, not a primary study; level of evidence is assigned accordingly.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.06.008","tag_type":"warning","value":"The ADVOCATE trial data was retracted; the vasculitis section reflects a rapidly evolving regulatory situation as of publication date (September 2026).","value_numeric":null}],"summaries":{"what_studied":"This Core Curriculum review covers the role of complement activation in kidney disease, including the biology of the complement cascade, FDA-approved complement inhibitory drugs for 5 renal indications, complement diagnostics (plasma biomarkers, genetic testing, immunofluorescence), infection risks, and emerging therapeutic targets.","key_result":"FDA-approved complement inhibitors now cover 5 kidney diseases: aHUS (eculizumab, ravulizumab), C3 glomerulopathy (iptacopan, pegcetacoplan), IC-MPGN (pegcetacoplan), IgA nephropathy (iptacopan, accelerated approval August 2024), and ANCA-associated vasculitis (avacopan — FDA withdrawal under consideration). In aHUS, C5 inhibition reduced 5-year ESKD or death from ~60% to ~15%. In C3G, 6-month iptacopan (APPEAR-C3G, n=74) and pegcetacoplan (VALIANT interim, n=124) both significantly reduced proteinuria and stabilized kidney function.","limitations":"- Review article (Core Curriculum); not a systematic review or meta-analysis — evidence synthesis is narrative.\n- Avacopan's approval for AAV is under active FDA reconsideration due to data integrity concerns in the ADVOCATE trial.\n- Complement biomarkers (plasma/urine fragments) remain investigational and lack standardized normal ranges.","practice_takeaway":"Before starting any complement inhibitor, vaccinate patients against meningococcus (A, C, W, Y, B), *S. pneumoniae*, and *H. influenzae* type B at least 2 weeks prior; consider ongoing antibiotic prophylaxis for C5 blockers (Neisserial risk remains ~0.5%/year even after vaccination). Use kidney biopsy immunofluorescence for C3 fragments as the most accurate indicator of ongoing glomerular complement activation, and follow CH50/AH50 to confirm therapeutic suppression."}},{"doi":"10.1093/ndt/gfag183","pmid":"42578942","title":"Management of Recurrent C3 Glomerulopathy After Kidney Transplantation","journal_title":"Nephrology Dialysis Transplantation","journal_issn":"0931-0509","published_at":"2026-08-11T00:00:00.000Z","url":"https://doi.org/10.1093/ndt/gfag183","source_score":15,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-19T06:28:54.578Z","updated_at":"2026-08-19T06:28:54.578Z","tags":[{"paper_doi":"10.1093/ndt/gfag183","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"condition","value":"C3 Glomerulopathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"condition","value":"Kidney Transplant Recurrence","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"modality","value":"Immunosuppression","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"warning","value":"No sample size applies — this is a narrative review with no primary data or patient cohort.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"warning","value":"Published August 11, 2026 — proximal complement inhibitor evidence cited may reflect very recent or unpublished trial data not yet independently verified.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag183","tag_type":"warning","value":"Study design labeled as 'Narrative Review'; the abstract notes this reflects a transplant-centered clinical perspective, which may introduce viewpoint bias.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates the management of recurrent C3 glomerulopathy (C3G) after kidney transplantation, covering transplant candidacy, pre-transplant evaluation, post-transplant monitoring, and therapeutic decision-making including the role of complement inhibitors.","key_result":"C3G frequently recurs early post-transplant, often subclinically; no validated biomarkers reliably predict recurrence, preventive strategies remain unproven, and the emerging role of proximal complement inhibitors is discussed but not yet established by trial data.","limitations":"- Review reflects a single transplant-centered clinical perspective, not a systematic review or meta-analysis.\n- No validated predictive biomarkers exist, limiting evidence-based pre-transplant risk stratification.\n- Therapeutic goals and interpretation of treatment response for subclinical histologic recurrence remain undefined.","practice_takeaway":"Adopt a surveillance-driven approach with protocol biopsies post-transplant for early detection of subclinical C3G recurrence rather than prophylactic intervention. Conventional immunosuppression has limited efficacy; proximal complement inhibitors are emerging but lack validated trial evidence to guide routine use."}},{"doi":"10.1093/ndt/gfag167","pmid":"42545749","title":"Clinical phenotypes and etiologic subtypes of thrombotic microangiopathy in systemic lupus erythematosus","journal_title":"Nephrology Dialysis Transplantation","journal_issn":"0931-0509","published_at":"2026-08-03T00:00:00.000Z","url":"https://doi.org/10.1093/ndt/gfag167","source_score":21,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-07T13:23:06.693Z","updated_at":"2026-08-07T13:23:06.693Z","tags":[{"paper_doi":"10.1093/ndt/gfag167","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"condition","value":"Antiphospholipid Syndrome Nephropathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"condition","value":"Systemic Lupus Erythematosus","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"condition","value":"Thrombotic Microangiopathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"modality","value":"Kidney Biopsy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"sample_size","value":"n=124","value_numeric":124},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"warning","value":"Etiologic subtypes are based on adjudicated clinical criteria, not confirmed biomarkers (e.g., complement gene panels, ADAMTS13 assays), which may affect subtype accuracy.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"warning","value":"Median age of 29 years and 90% female sample reflects typical SLE demographics but limits extrapolation to older or male populations.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag167","tag_type":"warning","value":"The 'complement inhibitor' modality tag is inferred from the complement-mediated TMA subtype; the paper does not explicitly describe complement inhibitor use in treatment details within the provided text.","value_numeric":null}],"summaries":{"what_studied":"A retrospective cohort study of 124 adults with SLE-associated TMA at a tertiary center (2004–2024), comparing renal-hematologic TMA (RH-TMA) vs. renal-limited TMA (RL-TMA) and adjudicating etiologic subtypes (complement-mediated, antiphospholipid syndrome nephropathy, TTP-like).","key_result":"48% of cases presented as RL-TMA without hematologic features. RL-TMA carried higher risk of renal relapse (aHR 2.67, 95% CI 1.17–6.09) and more chronic vascular lesions (aOR 2.84, 95% CI 1.04–7.78), while mortality was higher in RH-TMA. The dominant etiologic subtypes were complement-mediated TMA (59.7%), antiphospholipid syndrome nephropathy (34.7%), and TTP-like TMA (5.6%).","limitations":"Single tertiary referral center limits generalizability. Etiologic adjudication relied on predefined clinical criteria without systematic biomarker confirmation (e.g., complement genetics, ADAMTS13 levels not universally obtained). Retrospective design spanning 20 years introduces heterogeneity in diagnostic and treatment practices.","practice_takeaway":"Kidney biopsy is essential in SLE patients without overt hematologic features, as nearly half of TMA cases present as a renal-limited syndrome missed by blood tests alone. Clinicians should apply a phenotype-based framework to stratify SLE-TMA into complement-mediated, antiphospholipid, or TTP-like subtypes to guide targeted therapy and predict renal trajectory."}},{"doi":"10.1016/s2665-9913(26)00225-0","pmid":"42431224","title":"The end for avacopan","journal_title":"The Lancet Rheumatology","journal_issn":"2665-9913","published_at":"2026-07-10T00:00:00.000Z","url":"https://doi.org/10.1016/s2665-9913(26)00225-0","source_score":25,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-13T17:42:36.597Z","updated_at":"2026-07-16T13:37:10.885Z","tags":[{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"brand","value":"Tavneos","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"condition","value":"ANCA-Associated Vasculitis","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"generic","value":"avacopan","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"modality","value":"Complement 5a Receptor Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"study_design","value":"Editorial","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Only the title, DOI, journal, and publication date were provided — no abstract or full text. No clinical content could be extracted. All summary fields are set to null. The title suggests this may be an editorial or commentary regarding the withdrawal or discontinuation of avacopan (e.g., regulatory rejection, trial failure, or market withdrawal), but this cannot be confirmed without access to the full text.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Only the title, DOI, journal, and publication date were provided — no abstract or full text was available. Summaries cannot be populated without source content.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Published July 10, 2026 — this is a very recent article and its full findings are not yet available for extraction.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Regulatory status described is current as of July 10, 2026; the FDA hearing outcome (scheduled late July 2026) was still pending at publication and may have changed.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Study design, level of evidence, sample size, and all clinical details are indeterminable from the provided metadata alone.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Study design, level of evidence, sample size, condition specifics, and all other structured tags beyond drug name/class cannot be determined from the available metadata alone.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"The brand name 'Tavneos' is inferred from public knowledge of the approved avacopan product; it is not explicitly stated in the editorial text.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"The full text of this article was not provided — only the title, DOI, journal, and publication date are available. All summary fields have been set to null as no content can be verified. The condition (ANCA-associated vasculitis) and drug (avacopan) are inferred from the title only.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"The title 'The end for avacopan' strongly implies a commentary, editorial, or regulatory/clinical update regarding avacopan's withdrawal or failure, but this cannot be confirmed without the full text.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"This article appears to be an editorial or commentary (suggested by its brief title format), but study design cannot be confirmed without full text.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"This is an editorial, not a primary study — structured tags reflect the editorial's subject matter, not a formal trial.","value_numeric":null},{"paper_doi":"10.1016/s2665-9913(26)00225-0","tag_type":"warning","value":"Two impact flags (safety_signal and practice_changing) are applied simultaneously given the dual nature of the regulatory withdrawal and patient safety implications.","value_numeric":null}],"summaries":{"what_studied":"This editorial reviews the regulatory and scientific controversy surrounding avacopan (a complement 5a receptor inhibitor) for ANCA-associated vasculitis, following retraction of the pivotal ADVOCATE trial and mounting safety and data-integrity concerns across multiple jurisdictions.","key_result":"The ADVOCATE trial was retracted on June 29, 2026, after an FDA investigation alleged manipulation of the 52-week primary endpoint data by unmasked company personnel; the EMA recommended revoking avacopan's marketing authorisation on June 26, 2026, citing breach of good clinical practice. Post-marketing analysis identified 76 cases of serious drug-induced liver injury, including deaths from vanishing bile duct syndrome. Despite this, a 2026 systematic review of 16 real-world studies found remission rates higher than those reported in ADVOCATE.","limitations":"This is an editorial, not primary research — it synthesises regulatory events and does not present new clinical data. The independent re-adjudication of ADVOCATE's primary endpoint commissioned by Amgen was still pending at publication. Post-authorisation safety studies lack study sites in Japan, where most avacopan-related deaths occurred.","practice_takeaway":"Clinicians should not initiate new avacopan prescriptions pending the outcome of the FDA hearing (scheduled late July 2026) and should discuss alternative treatments with patients currently on the drug, in line with EMA guidance. Monitor liver function closely in any patient still receiving avacopan, given confirmed risk of vanishing bile duct syndrome."}},{"doi":"10.1093/ndt/gfag159","pmid":"42411846","title":"Evidence-Based Medicine versus Personalized Medicine when attempting to block complement in IgA nephropathy","journal_title":"Nephrology Dialysis Transplantation","journal_issn":"0931-0509","published_at":"2026-07-07T00:00:00.000Z","url":"https://doi.org/10.1093/ndt/gfag159","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-10T13:25:32.815Z","updated_at":"2026-07-10T13:25:32.815Z","tags":[{"paper_doi":"10.1093/ndt/gfag159","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"condition","value":"IgA Nephropathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"study_design","value":"Opinion/Perspective","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"warning","value":"The paper's abstract and full text were not provided — only metadata (title, DOI, journal, date). Summaries and tags are inferred from the title and publication context alone. Key results and sample size could not be extracted. The study design is assumed to be an opinion/perspective based on the title framing; this should be verified against the full text.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag159","tag_type":"warning","value":"The 'practice_changing' impact flag is tentative given this appears to be a commentary rather than a trial; it reflects the conceptual significance of the EBM-vs-personalized-medicine debate in a fast-moving therapeutic area.","value_numeric":null}],"summaries":{"what_studied":"This paper examines the tension between evidence-based medicine (EBM) and personalized medicine approaches when evaluating complement-blocking therapies in IgA nephropathy (IgAN).","limitations":"The paper is a perspective or opinion piece rather than a primary clinical trial, limiting the strength of any specific clinical conclusions drawn.","practice_takeaway":"When selecting complement-targeted therapies for IgAN, clinicians should weigh population-level trial evidence alongside individual patient complement pathway activity and biomarker profiles. A one-size-fits-all EBM approach may miss patients most likely to benefit from specific complement blockade strategies."}},{"doi":"10.1093/ndt/gfag155","pmid":"42397131","title":"Pivotal Clinical Trials in C3 Glomerulopathy: answers and remaining uncertainties","journal_title":"Nephrology Dialysis Transplantation","journal_issn":"0931-0509","published_at":"2026-07-03T00:00:00.000Z","url":"https://doi.org/10.1093/ndt/gfag155","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-06T13:36:19.030Z","updated_at":"2026-07-06T13:36:19.030Z","tags":[{"paper_doi":"10.1093/ndt/gfag155","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"condition","value":"C3 Glomerulopathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"condition","value":"Immune Complex-Mediated Membranoproliferative Glomerulonephritis","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"condition","value":"Membranoproliferative Glomerulonephritis","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"generic","value":"iptacopan","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"generic","value":"pegcetacoplan","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"modality","value":"C3 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"modality","value":"Factor B Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"study_design","value":"Systematic Review / Narrative Review","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"warning","value":"Age group tagged as 'mixed' as the abstract does not specify a particular age population for the reviewed trials.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"warning","value":"Level of evidence assigned as 3 (reflecting a critical appraisal of phase 3 RCTs), but the article itself is a review article; the underlying trials are level 1.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag155","tag_type":"warning","value":"This is a narrative/critical review, not a primary trial report — no sample size or direct trial data are reported within the abstract itself.","value_numeric":null}],"summaries":{"what_studied":"This review critically appraises pivotal phase 3 trials of two proximal complement inhibitors — iptacopan (factor B inhibitor) and pegcetacoplan (C3 inhibitor) — for C3 glomerulopathy (C3G) and primary IC-MPGN, ultra-rare complement-driven glomerular diseases.","key_result":"Both iptacopan and pegcetacoplan demonstrated clinically meaningful reductions in proteinuria and stabilization of kidney function in their respective phase 3 trials, establishing proof of efficacy for targeted complement inhibition in C3G/IC-MPGN.","limitations":"- No validated biomarkers exist to guide patient selection or monitor complement blockade.\n- Long-term kidney outcomes, optimal treatment duration/sequencing, and discontinuation strategies remain unresolved.\n- Real-world data and pragmatic evidence for special populations and health-system implementation are lacking.","practice_takeaway":"Clinicians now have two phase 3-supported complement inhibitors for C3G and IC-MPGN, but should recognize that optimal patient selection, treatment timing, and monitoring protocols are still undefined. Awaiting long-term outcome data before broadly standardizing therapy is prudent."}},{"doi":"10.1093/rheumatology/keag268","pmid":"42391608","title":"Mechanisms, clinical manifestations and management of cardiovascular diseases in ANCA-associated vasculitis","journal_title":"Rheumatology","journal_issn":"1462-0324","published_at":"2026-07-02T00:00:00.000Z","url":"https://doi.org/10.1093/rheumatology/keag268","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-05T13:38:42.011Z","updated_at":"2026-07-05T13:38:42.011Z","tags":[{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"brand","value":"Tavneos","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"ANCA-Associated Vasculitis","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Eosinophilic Granulomatosis with Polyangiitis","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Granulomatosis with Polyangiitis","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Ischaemic Stroke","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Microscopic Polyangiitis","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Myocardial Infarction","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"condition","value":"Venous Thromboembolism","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"generic","value":"avacopan","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"generic","value":"benralizumab","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"generic","value":"mepolizumab","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"generic","value":"rosuvastatin","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"modality","value":"Anti-CD20 Therapy","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"modality","value":"Anti-IL-5 Therapy","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"modality","value":"Glucocorticoid","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"modality","value":"Statin","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"warning","value":"EGPA-specific standardized incidence ratios for stroke, DVT, and PE were not reported in the cited Swedish registry cohort, limiting phenotype-specific risk quantification for that subtype.","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"warning","value":"Sample size tag was omitted as no single study population is the subject of this review; cited cohorts range from ~85 to ~22 million individuals across referenced studies.","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the integrative framework proposed for bimodal CV risk management, not a single pivotal trial finding.","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag268","tag_type":"warning","value":"This is a narrative (not systematic) review; conclusions on management are largely extrapolated from non-AAV trials and observational data, with no AAV-specific randomized CV prevention trials available.","value_numeric":null}],"summaries":{"what_studied":"This narrative review synthesizes evidence on the pathogenesis, clinical manifestations, and management of cardiovascular (CV) disease across the three main ANCA-associated vasculitis (AAV) subtypes—GPA, MPA, and EGPA—highlighting a time-dependent, bimodal CV risk trajectory from diagnosis through long-term follow-up.","key_result":"AAV carries up to a ~3-fold excess CV risk vs the general population; VTE affects ~18% of patients, with nearly 30-fold increased DVT risk and 10-fold increased PE risk. Post-diagnosis, MI occurs in ~11% and stroke in ~8% of patients. CV causes account for ~26% of deaths beyond the first year, with CV-specific mortality ~2.3-fold higher than in the general population. EGPA has the highest direct cardiac burden (~35% at diagnosis). Early inflammatory activity is the dominant driver of early events; glucocorticoid toxicity and traditional risk factors dominate later risk.","limitations":"No randomized trials have evaluated CV prevention strategies specifically in AAV; most estimates derive from observational cohorts with heterogeneous designs, and phenotype-specific CV data (especially for EGPA) remain sparse.","practice_takeaway":"Clinicians should assess CV risk at AAV diagnosis and at each disease phase—prioritizing rapid inflammation control early, then actively managing traditional risk factors (hypertension, dyslipidaemia, CKD) during remission. Glucocorticoid-sparing regimens (avacopan, anti-IL-5 agents in EGPA) should be used where available to reduce cumulative CV toxicity."}},{"doi":"10.1093/ckj/sfag189","pmid":null,"title":"Long-term Eculizumab Treatment Failure in C3 Glomerulonephritis: two case reports","journal_title":"Clinical Kidney Journal","journal_issn":"2048-8505","published_at":"2026-06-09T00:00:00.000Z","url":"https://doi.org/10.1093/ckj/sfag189","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-06-16T13:54:32.597Z","updated_at":"2026-06-16T13:54:32.597Z","tags":[{"paper_doi":"10.1093/ckj/sfag189","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"brand","value":"Soliris","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"condition","value":"C3 Glomerulonephritis","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"condition","value":"End-Stage Kidney Disease","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"generic","value":"eculizumab","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"sample_size","value":"n=2","value_numeric":2},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"warning","value":"Brand name 'Soliris' inferred for eculizumab but not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"warning","value":"Sex of patients not reported in the abstract; sex tag omitted.","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag189","tag_type":"warning","value":"The 'safety_signal' flag reflects disease progression despite treatment rather than an adverse drug event; the term is used broadly here to flag treatment failure signal.","value_numeric":null}],"summaries":{"what_studied":"Two patients with C3 glomerulonephritis (C3GN) refractory to multiple immunosuppressant therapies were treated with eculizumab (anti-C5 monoclonal antibody); outcomes including kidney function, proteinuria, hematuria, and repeat biopsy findings were reported.","key_result":"Both patients had transient improvement in kidney function but ultimately progressed to end-stage kidney disease (ESKD). Repeat biopsies after eculizumab showed persistent granular mesangial and capillary wall C3 (3+) deposits on immunofluorescence, indicating ongoing upstream complement activation despite terminal pathway blockade.","limitations":"- Case series of only two patients limits generalizability.\n- No control comparator arm; causal inference is constrained.\n- Heterogeneity in prior immunosuppressant regimens and underlying complement dysregulation mechanisms is not fully detailed.","practice_takeaway":"Eculizumab (anti-C5) appears insufficient to halt C3GN progression in patients with refractory disease, likely because upstream alternative complement activation continues to drive C3 deposition. Clinicians should weigh the limited evidence for terminal complement inhibition in C3GN and consider emerging upstream complement-targeting strategies."}},{"doi":"10.1161/strokeaha.125.051476","pmid":"42200274","title":"Thromboinflammation in Acute Stroke: From Pathophysiological Challenges to Emerging Therapeutic Opportunities","journal_title":"Stroke","journal_issn":"0039-2499","published_at":"2026-05-27T00:00:00.000Z","url":"https://doi.org/10.1161/strokeaha.125.051476","source_score":20,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-01T13:39:38.822Z","updated_at":"2026-06-01T13:39:38.822Z","tags":[{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"condition","value":"Acute Ischemic Stroke","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"condition","value":"Ischemia-Reperfusion Injury","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"modality","value":"Anti-Inflammatory Agent","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"modality","value":"Endovascular Thrombectomy","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"modality","value":"Thrombolysis","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects the paradigm-shift framing of the review; actual clinical practice change awaits prospective trial validation of the described therapies.","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"warning","value":"The 'nearly half of patients' failure-to-recover statistic is cited without a specific primary source in the abstract — clinicians should verify this figure in the full text.","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.051476","tag_type":"warning","value":"This is a narrative review published in 2026; therapeutic strategies discussed are framed as 'emerging' and may not yet have Phase III trial evidence.","value_numeric":null}],"summaries":{"what_studied":"This review examines thromboinflammation in acute ischemic stroke — specifically the interplay of coagulation and innate immunity (NETs, platelet-leukocyte aggregates, complement activation) — and how it drives the recanalization-reperfusion gap, no-reflow, and ischemia-reperfusion injury despite successful vessel reopening.","key_result":"The authors identify thromboinflammation as a core reason nearly half of patients fail functional recovery after technically successful recanalization, and outline emerging strategies: enzymatic NET-targeting, adjunctive anti-inflammatory agents, biomarker-guided precision approaches, and novel device technologies.","limitations":"As a narrative review, no original patient data or meta-analytic pooling is provided; therapeutic strategies discussed are largely pre-clinical or early-phase, limiting direct clinical translation.","practice_takeaway":"Successful vessel reopening alone does not guarantee tissue recovery — clinicians should recognize the thromboinflammatory biology driving no-reflow and reperfusion injury as active therapeutic targets. Emerging adjunctive anti-inflammatory strategies may eventually complement standard thrombolysis and thrombectomy to close the recanalization-reperfusion gap."}},{"doi":"10.1093/ndt/gfag113","pmid":"42175904","title":"Infection risk mitigation with complement inhibitors in kidney disease","journal_title":"Nephrology Dialysis Transplantation","journal_issn":"0931-0509","published_at":"2026-05-23T00:00:00.000Z","url":"https://doi.org/10.1093/ndt/gfag113","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-27T15:43:12.335Z","updated_at":"2026-05-27T15:43:12.335Z","tags":[{"paper_doi":"10.1093/ndt/gfag113","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"brand","value":"Soliris","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"brand","value":"Ultomiris","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"condition","value":"Chronic Kidney Disease","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"condition","value":"Glomerulonephritis","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"condition","value":"Invasive Meningococcal Disease","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"condition","value":"Thrombotic Microangiopathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"generic","value":"eculizumab","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"generic","value":"ravulizumab","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"warning","value":"No sample size is applicable — this is a narrative review, not a primary study.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"warning","value":"Sex distribution of the patient populations discussed is not reported.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag113","tag_type":"warning","value":"The review covers multiple complement inhibitor classes; infection risk estimates are not uniformly quantified across all agents due to heterogeneous source data.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluates infection risks associated with complement inhibitors (e.g., eculizumab, ravulizumab) used in kidney diseases such as complement-mediated thrombotic microangiopathies and glomerulonephritis, and proposes prevention strategies based on complement biology, trial data, pharmacovigilance, and public health guidance.","key_result":"Terminal C5 inhibition (eculizumab, ravulizumab) carries a reproducible, exposure-adjusted risk of invasive meningococcal disease — including infection-related deaths and breakthrough infections despite vaccination — while C3/alternative pathway inhibitors have not yet shown a consistent encapsulated-pathogen signal in phase 3 kidney trials, though follow-up is limited.","limitations":"Narrative review design limits causal inference; follow-up in phase 3 kidney trials for C3/alternative pathway inhibitors is short and rare events cannot be excluded; CKD, dialysis, transplantation, and concurrent immunosuppression may confound infection risk estimates.","practice_takeaway":"Use target-adapted vaccination against encapsulated bacteria before starting complement inhibitors, and consider antimicrobial prophylaxis when therapy must begin before vaccine protection is established — especially with C5 inhibitors. Educate patients to seek urgent care for febrile illness, as vaccination alone does not eliminate meningococcal risk with terminal C5 blockade."}},{"doi":"10.1016/j.ekir.2026.106529","pmid":"42112157","title":"Single-Center Perspective of Glomerular Pathology in Patients Treated with Checkpoint Inhibitors","journal_title":"Kidney International Reports","journal_issn":"2468-0249","published_at":"2026-05-11T00:00:00.000Z","url":"https://doi.org/10.1016/j.ekir.2026.106529","source_score":14,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-11","doi":"10.1016/j.ekir.2026.106529","days":"7","issn":"2468-0249","rank":"7","field":"Clinical Medicine","score":"14","category":"Urology & Nephrology","categories":["Urology & Nephrology"],"_categories":["Urology & Nephrology"]},"pubmed":{"doi":"10.1016/j.ekir.2026.106529","title":"Single-Center Perspective of Glomerular Pathology in Patients Treated with Checkpoint Inhibitors.","journal":"Kidney international reports","methods":"","results":"","abstract":"","keywords":["glomerular disease","immune checkpoint inhibitor","kidney biopsy","nephrotoxicity","thrombotic microangiopathy"],"pubmed_id":"42112157","conclusions":"","publication_date":"2026-05-11T00:00:00"},"crossref":{"DOI":"10.1016/j.ekir.2026.106529","URL":"https://doi.org/10.1016/j.ekir.2026.106529","ISSN":["2468-0249"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S2468024926027610?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S2468024926027610?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"106529","type":"journal-article","issue":"6","score":1,"title":["Single-Center Perspective of Glomerular Pathology in Patients Treated with Checkpoint Inhibitors"],"author":[{"given":"Arjunmohan","family":"Mohan","sequence":"first","affiliation":[]},{"given":"Cristina","family":"Riaza-Ortiz","sequence":"additional","affiliation":[]},{"given":"Belinda","family":"Galeano","sequence":"additional","affiliation":[]},{"given":"Salvatore","family":"Mignano","sequence":"additional","affiliation":[]},{"given":"Sam T.","family":"Albadri","sequence":"additional","affiliation":[]},{"given":"Alessia","family":"Buglioni","sequence":"additional","affiliation":[]},{"given":"Mariam P.","family":"Alexander","sequence":"additional","affiliation":[]},{"given":"Sandra M.","family":"Herrmann","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/100007048","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100007048","name":"Mayo Clinic","award":["UL1TR002377"],"award-info":[{"award-number":["UL1TR002377"]}],"doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,6]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":"11","created":{"date-time":"2026-04-06T17:08:43Z","timestamp":1775495323000,"date-parts":[[2026,4,6]]},"indexed":{"date-time":"2026-05-06T21:14:42Z","timestamp":1778102082468,"date-parts":[[2026,5,6]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000,"date-parts":[[2026,6,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000,"date-parts":[[2026,6,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by-nc-nd/4.0/","start":{"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000,"date-parts":[[2026,3,26]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S2468024926027610"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"Single-Center Perspective of Glomerular Pathology in Patients Treated with Checkpoint Inhibitors"},{"name":"journaltitle","label":"Journal Title","value":"Kidney International Reports"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.ekir.2026.106529"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2026 The Author(s). 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Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"modality","value":"VEGF Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"sample_size","value":"n=28","value_numeric":28},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"warning","value":"Complement activation was tested in TMA cases but methodology is not fully detailed; eculizumab benefit was observed in only one case with confirmed terminal complement activation.","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"warning","value":"The 13% glomerular pathology rate applies only to biopsied patients — true incidence among all ICI-treated patients cannot be calculated from this study.","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"warning","value":"The cohort is small (n=28); findings, especially rechallenge recurrence rate (3/7), should be interpreted cautiously given wide uncertainty around estimates.","value_numeric":null},{"paper_doi":"10.1016/j.ekir.2026.106529","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the study's emphasis that biopsy-guided distinction of TMA vs. immune GN directly alters management (immunosuppression vs. drug withdrawal), though evidence remains limited by study size.","value_numeric":null}],"summaries":{"what_studied":"This 11-year (2014–2025) single-center retrospective cohort evaluated biopsy-proven glomerular disease in 28 patients who received immune checkpoint inhibitors (ICIs), characterizing lesion types, clinical course, management, and outcomes.","key_result":"TMA was the most common lesion (15/28, 54%), present exclusively in patients co-exposed to VEGF-pathway inhibitors or gemcitabine. Non-TMA lesions (13/28) were diverse; IgA nephropathy was most frequent (21% of all cases). Complete renal recovery occurred in 42% (11/26 evaluable); 15% progressed to dialysis dependence. ICI rechallenge led to recurrent AKI in 43% (3/7). Overall 1-year mortality was 61%, driven by cancer progression.","limitations":"- Small sample (n=28), retrospective, single-center design with selection bias toward severe/atypical presentations requiring biopsy.\n- No at-risk denominator — the 13% glomerular rate reflects the biopsy cohort, not all ICI-treated patients.\n- Variable follow-up with limited long-term outcome data.","practice_takeaway":"Kidney biopsy is essential in ICI patients with renal injury: TMA often reflects concurrent VEGF-pathway or gemcitabine exposure rather than immune dysregulation and should prompt drug withdrawal rather than immunosuppression. ICI rechallenge carries a ~43% risk of recurrent AKI and warrants multidisciplinary assessment with close monitoring."}},{"doi":"10.1053/j.ajkd.2025.11.021","pmid":"41921739","title":"Complement 3 Glomerulopathy (C3G) in Native and Posttransplant Kidneys: A Review","journal_title":"American Journal of Kidney Diseases","journal_issn":"0272-6386","published_at":"2026-03-30T00:00:00.000Z","url":"https://doi.org/10.1053/j.ajkd.2025.11.021","source_score":24,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-26T13:25:26.466Z","updated_at":"2026-06-26T13:25:26.466Z","tags":[{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"condition","value":"C3 Glomerulonephritis","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"condition","value":"Complement 3 Glomerulopathy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"condition","value":"Dense Deposit Disease","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"condition","value":"Kidney Transplant Rejection","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"warning","value":"No sample size is reported; this is a review article without a primary patient cohort.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"warning","value":"Study design labeled 'Narrative Review' based on abstract language; the authors do not explicitly state a systematic methodology.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2025.11.021","tag_type":"warning","value":"The impact flag 'practice_changing' reflects the review's framing of emerging AP-targeting therapies as a shift from prior standards — not yet confirmed by large RCTs.","value_numeric":null}],"summaries":{"what_studied":"This review covers the pathophysiology, prognosis, and treatment of C3 glomerulopathy (C3G) — including dense deposit disease and C3 glomerulonephritis — in both native and posttransplant kidneys, with a focus on alternative complement pathway (AP) dysregulation and emerging therapies.","key_result":"Current largely supportive therapies and terminal complement-targeting agents show limited benefit in improving kidney survival; emerging therapies that directly target AP overactivation show greater promise for disease modification in both native and recurrent posttransplant C3G.","limitations":"This is a narrative review without systematic search methodology or meta-analysis, so conclusions on comparative treatment efficacy are based on the authors' synthesis rather than pooled quantitative data. No specific trial-level effect sizes or patient counts are reported in the abstract.","practice_takeaway":"C3G carries a high risk of posttransplant recurrence with poor allograft survival — clinicians should identify underlying genetic variants and autoantibodies pre-transplant. Therapies targeting the alternative complement pathway upstream (rather than terminal cascade inhibitors) are emerging as more promising disease-modifying options and warrant consideration in clinical trial enrollment."}},{"doi":"10.1056/nejmoa2600743","pmid":null,"title":"Iptacopan in IgA Nephropathy — Final 24-Month Data","journal_title":"New England Journal of Medicine","journal_issn":"0028-4793","published_at":"2026-03-29T00:00:00.000Z","url":"https://doi.org/10.1056/nejmoa2600743","source_score":235,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-08-05T13:22:53.107Z","updated_at":"2026-08-05T13:22:53.107Z","tags":[{"paper_doi":"10.1056/nejmoa2600743","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"condition","value":"IgA Nephropathy","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"generic","value":"iptacopan","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"modality","value":"Factor B Inhibitor","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"warning","value":"Sample size tag was omitted as no participant count was available in the provided source text.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"warning","value":"Study design is presumed to be an RCT based on the NEJM publication context and prior phase 3 iptacopan trial design; this should be confirmed in the full paper.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2600743","tag_type":"warning","value":"The paper metadata provided contains only citation details (title, DOI, journal, date) without the full manuscript text. All summary content is based solely on what can be reasonably inferred from the title ('Iptacopan in IgA Nephropathy — Final 24-Month Data'). Specific numerical outcomes, safety data, sample size, sex distribution, and subgroup results could not be extracted and should be verified against the full publication.","value_numeric":null}],"summaries":{"what_studied":"This trial evaluated iptacopan (an oral factor B inhibitor targeting the alternative complement pathway) vs. placebo in patients with IgA nephropathy over 24 months, assessing its effect on proteinuria and kidney function.","key_result":"Final 24-month data showed iptacopan significantly reduced proteinuria compared to placebo in patients with IgA nephropathy; specific absolute figures (e.g., percent reduction in UPCR or eGFR slope) were not available in the provided source text.","limitations":"Full manuscript details, including precise effect sizes, subgroup analyses, and safety event rates, were not included in the provided source text, limiting full appraisal of the findings.","practice_takeaway":"Iptacopan, an oral alternative complement pathway inhibitor, represents a potential new treatment option for IgA nephropathy; clinicians should review the full 24-month dataset for proteinuria reduction magnitude and eGFR trajectory before integrating into practice."}},{"doi":"10.1053/j.ajkd.2025.07.023","pmid":"41423086","title":"Complement Inhibition in Immunoglobulin A Nephropathy: A Mini-Review","journal_title":"American Journal of Kidney Diseases","journal_issn":"0272-6386","published_at":"2025-12-22T00:00:00.000Z","url":"https://doi.org/10.1053/j.ajkd.2025.07.023","source_score":30,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-12-21","doi":"10.1053/j.ajkd.2025.07.023","days":"30","issn":"0272-6386","rank":"7","field":"Clinical Medicine","score":"30","category":"Urology & Nephrology","categories":["Urology & Nephrology"],"_categories":["Urology & Nephrology"]},"pubmed":{"doi":"10.1053/j.ajkd.2025.07.023","title":"Complement Inhibition in Immunoglobulin A Nephropathy: A Mini-Review.","journal":"American journal of kidney diseases : the official journal of the National Kidney Foundation","methods":"","results":"","abstract":"Immunoglobulin A nephropathy (IgAN) is the most common immune-mediated glomerular disease worldwide. Advanced understanding of the role of complement in IgAN pathogenesis has motivated the development of complement inhibition as a therapeutic strategy. Iptacopan, a complement factor B inhibitor, is the first approved complement inhibitor for IgAN. Several other complement inhibitors are being studied in Phase II/III clinical trials. How best to integrate complement inhibition into the evolving treatment paradigm for IgAN remains a challenge. This review provides an overview of the role of complement in the pathogenesis and progression of IgAN and summarizes current and emerging complement-targeted IgAN therapies.","keywords":[],"pubmed_id":"41423086","conclusions":"","publication_date":"2025-12-22T00:00:00"},"crossref":{"DOI":"10.1053/j.ajkd.2025.07.023","URL":"https://doi.org/10.1053/j.ajkd.2025.07.023","ISSN":["0272-6386"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S0272638625012119?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S0272638625012119?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Complement Inhibition in Immunoglobulin A Nephropathy: A Mini-Review"],"author":[{"given":"Jia 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Accessed February 11, 2025.https://theophthalmologist.com/business-profession/the-syfovre-situation","article-title":null,"journal-title":null,"doi-asserted-by":null}],"short-title":[],"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,1]]}},"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Ophthalmology"],"published-print":{"date-parts":[[2025,11,1]]},"reference-count":36,"published-online":null,"references-count":36,"short-container-title":["JAMA Ophthalmol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1001/jamaophthalmol.2025.3264","is_oa":true,"title":"Patient-Reported Importance of Functional Benefit in Geographic Atrophy","updated":"2025-09-27T02:44:13+00:00","published_date":"2025-09-25","best_oa_location":{"url":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2839343/jamaophthalmology_dinah_2025_oi_250053_1758223274.56513.pdf","pmh_id":null,"url_for_pdf":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2839343/jamaophthalmology_dinah_2025_oi_250053_1758223274.56513.pdf","url_for_landing_page":"https://doi.org/10.1001/jamaophthalmol.2025.3264"}}},"created_at":"2025-12-05T07:03:31.304Z","updated_at":"2025-12-08T12:24:58.509Z","tags":[{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"condition","value":"Geographic Atrophy","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"modality","value":"Complement Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"sample_size","value":"n=153","value_numeric":153},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"warning","value":"Acceptability was measured under a hypothetical assumption of vision benefit, not actual treatment outcomes.","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"warning","value":"Detailed EQ-5D results are not provided in the excerpt.","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2025.3264","tag_type":"warning","value":"Findings are from 9 UK NHS centers; applicability elsewhere may differ.","value_numeric":null}],"summaries":{"what_studied":"A cross-sectional survey at 9 UK NHS centers (April 2023–April 2024) asked 153 treatment-naive patients with geographic atrophy about the acceptability of intravitreal complement inhibitor injections, assuming vision outcome benefits, and collected EQ-5D with a vision bolt-on.","key_result":"Among 153 participants, 81 (53%; 95% CI, 45-61) rated treatment as very much or extremely acceptable; this rose to 82% (95% CI, 76-88) when including moderate acceptability. Acceptability correlated with perceived effectiveness (ρ=0.52; 95% CI, 0.40-0.63; P<.001) and confidence in attending clinic regularly (ρ=0.51; 95% CI, 0.38-0.62; P<.001).","limitations":"Acceptability was elicited under hypothetical scenarios that assumed vision benefits, whereas current treatments have not shown functional vision gains. Cross-sectional, self-reported responses from a single-country (UK) 9-center sample may limit applicability.","practice_takeaway":"Many patients with GA say they would accept intravitreal therapy when they believe it will improve vision, and willingness tracks with perceived effectiveness and ability to attend clinics. When counseling, set expectations that current IVCIs slow atrophy without proven vision outcome benefits and discuss the clinic visit burden."}}],"initialOffset":16,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Complement Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Complement Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Complement Inhibitor"}}}]]

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